In the practice of medicine there are many diagnostic and therapeutic procedures which require the insertion of a medical device into the human body through an orifice or tissue or contact of a medical device with blood or tissue. Such devices include guidewires; catheters, including Foley, angioplasty, diagnostic, and balloon catheters; implant devices; contact lenses; IUDs; peristaltic pump chambers; endotracheal tubes; gastroenteric feed tubes; arteriovenous shunts; condoms; and oxygenator and kidney membranes. It is necessary for the surface of these medical devices to have a low coefficient of friction to prevent injury, irritation, or inflammation to the patient and to facilitate medical and surgical procedures.
There is a need in the art for medical devices with the appropriate degree of slipperiness. The appropriate level is one at which the device is very slippery when contacted with the patient's moist tissue, but is not so slippery when dry that it is difficult for medical personnel to handle. Current materials from which such medical devices are made include silicone rubber, Teflon®, polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyurethane (PU), polytetrafluoroethylene (PTFE), Nylon®, polyethylene terephthalate (PET), and glass. These materials, however, lack the desired degree of slipperiness.
One approach to providing medical devices with more desirable surface characteristics is to coat the devices made from existing materials with various coating compositions. These coatings may be applied by spraying or painting the coating on the device or by dipping the device in a solution of the coating. Some substances which have been employed as coatings are Teflon®, silicone fluid, glycerin, mineral oils, olive oil, K-Y jelly, and fluorocarbons. However, these substances have not been entirely satisfactory because they lack hydrophilicity, are not retained on the device surface during the period of use, are non-durable, or exhibit inadequate retention of lubricity.
Hydrophilic polymer and hydrogel coatings were an improvement to the art and have been used successfully to provide coatings for many of the easier to coat substrates, such as polyurethane and latex rubber. These coatings, however, are poorly adherent to silicone rubber and wash off when the device is wetted.
Many medical devices such as guidewires, catheters, implant devices, contact lenses, IUDs, peristaltic pump chambers, endotracheal tubes, gastroenteric feed tubes, arteriovenous shunts, condoms, and oxygenator and kidney membranes are made from silicone rubber or other difficult to coat materials, such as Teflon®, polyethylene and polypropylene. Thus, there is a special need in the art for hydrophilic coatings for these and similarly difficult to coat substrates.
Adherence of previously known coatings to such surfaces is difficult because the coatings do not form covalent bonds with the silicone. As a result, the coatings have poor adherence, reduced durability, and poor resistance to wet abrasion.
Various polymers have been employed as coatings for medical devices. These include polyethylene oxide (PEO), polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), and polyurethane (PU). PEO and PEG are friction-reducing, blood-compatible polymers that are commercially available in a variety of molecular weights. Both have been used in combination with various other materials to produce lubricious coatings for medical devices. For example, coatings incorporating PEO and isocyanates are known in the art (U.S. Pat. Nos. 5,459,317, 4,487,808, and 4,585,666 to Lambert; and U.S. Pat. No. 5,558,900 to Fan et al.). In addition, polyols may be incorporated into such PEO/isocyanate coatings to produce a crosslinked polyurethane (PU) network entrapping the PEO (U.S. Pat. Nos. 5,077,352 and 5,179,174 to Elton). PEO has also been combined with structural plastic having a high molecular weight to produce a coating with reduced friction (U.S. Pat. No. 5,041,100 to Rowland).
None of these coatings are acceptable for coating silicone rubber and other difficult to coat substrates. Because these coatings do not form covalent linkages with the silicone surface of the substrate, they have poor adherence and durability and are easily washed from the surface when the substrate is wetted.
Another polymer used to coat medical devices is polyvinyl pyrrolidone (PVP). PVP may be used as a coating alone or in combination with other polymers. For example, polyvinyl pyrrolidone may be bonded to a substrate by thermally activated free radical initiators, UV light activated free-radical initiators, or E-beam radiation (WO 89/09246). One disadvantage of using such coatings is that E-beam radiation can be deleterious to some of the materials used in medical devices.
PVP may be used in conjunction with other polymers. One such coating is made from PVP and glycidyl acrylate. This coating requires the presence of amino groups on the surface of the substrate to react with the epoxy groups of the glycidyl acrylate to covalently bond the PVP-containing copolymer to the substrate (Nagoacha et al., Biomaterials, 419 (1990)). Silicone rubber does not contain any free amino groups, and thus this type of coating cannot form covalent bonds with the surface of the silicone substrate, resulting in poor adhesion.
Other coatings are composed of a mixture of PVP and polyurethane. These coatings provide low friction surfaces when wet. One such coating is a polyvinyl pyrrolidone-polyurethane interpolymer (U.S. Pat. Nos. 4,100,309 and 4,119,094 to Micklus et al.). Another such coating is composed of hydrophilic blends of polyvinyl pyrrolidone (PVP) and linear preformed polyurethanes (U.S. Pat. No. 4,642,267 to Cresy). In addition, PVP may be incorporated into a PU network by combining a polyisocyanate and a polyol with a PVP solution (U.S. Pat. Nos. 5,160,790 and 5,290,585 to Elton). Still another such coating is composed of two layers: a primer and a top coat. The primer coat is a polyurethane prepolymer containing free isocyanate groups, while the top coat is a hydrophilic copolymer of PVP and a polymer having active hydrogen groups, such as acrylamide (U.S. Pat. No. 4,373,009 to Winn).
None of these PVP based coatings are acceptable for coating silicone rubber and other difficult to coat substrates. Because these coatings do not form covalent linkages with the silicone surface of the substrate, they have poor adherence and durability and are easily washed from the surface when the substrate is wetted.
Hydrophilic polyurethanes have also been used in formulations other than with PVP as coatings for medical devices. For example, the prior art discloses coatings composed of polyurethane hydrogels containing a random mixture of polyisocyanates and a polyether dispersed in an aqueous liquid phase (U.S. Pat. No. 4,118,354 to Harada et al.). Polyurethanes have also been used as coatings in compositions containing chain-extended hydrophilic thermoplastic polyurethane polymers with a variety of hydrophilic high molecular weight non-urethane polymers (U.S. Pat. No. 4,990,357 to Karkelle et al.). It is also known to mix urethane with a silicone or siloxane emulsion. The carboxylic acid groups of the substrate and coating may then be linked with a cross-linking agent, such as a polyfunctional aziridine (U.S. Pat. No. 5,026,607 to Kiezulas).
Because the urethane and non-urethane polymers cannot react with one another or the surface to be coated, the resulting coatings have poor adhesion, especially to silicone surfaces. Also, since silicone surfaces do not contain free carboxylic acid groups, a crosslinker such as a polyfunctional aziridine will not covalently bond known coatings to the surface of a silicone substrate.
Additionally, there are many instances in which is it convenient or desirable to provide an active agent to a surface by coating the surface with the active agent. For example, antimicrobial activity can be provided to the surface of an article by coating the article with an antimicrobial metal or an organic antimicrobial agent.
Medical devices have conventionally been coated, for example, with silver and silver salts. (U.S. Pat. Nos. 5,395,651; 5,747,178; and 5,320,908 to Sodervall et al.; U.S. Pat. No. 4,054,139 to Crossley; U.S. Pat. Nos. 4,615,705 and 4,476,590 to Scales; and U.S. Pat. No. 4,581,028 to Fox). However, when the silver or silver salt is deposited directly onto an article, or incorporated within the article during manufacture, it is often difficult to control the amount of silver deposited or retained on the article surface. It is also difficult to control the retention or release of the silver from the surface of the article, making accurate and sustained dosing difficult.
Another conventional approach to providing infection-resistant surfaces has been the use of organic antimicrobial agents, such as biguanides. The most commonly used biguanides are chlorhexidine and its salts and derivatives. (U.S. Pat. Nos. 4,999,210; 5,013,306; and 5,707,366 to Solomon et al.) Additionally, combinations of oligodymanic metals or metal salts and chlorhexidine have been used to coat medical devices.
Yet another approach to preventing infection associated with medical devices has been the use of aluminosilicates or zeolites that contain ions of oligodynamic metals. Aluminosilicates and zeolites contain exchangeable ions. These ions can be exchanged with ions of the desired antimicrobial metal from a salt of the metal. (U.S. Pat. Nos. 4,525,410; 4,775,585; 4,911,898; and 4,911,899 to Hagiwara et al.; U.S. Pat. No. 5,064,599 to Ando et al.; and U.S. Pat. Nos. 4,938,955 and 5,556,699 to Niira et al.)
To overcome some of the disadvantages associated with these conventional antimicrobial coatings, coatings have been prepared by incorporating the antimicrobial agents described above into polymeric compositions. For example, metal ions and silicon dioxide have been coated on the surface of a silica gel that is used as a coating for medical devices. (U.S. Pat. No. 5,827,524 to Hagiwara et al.).
Additionally, metal ions have been incorporated into coatings of hydrophobic polymers. (U.S. Pat. Nos. 4,603,152 and 4,677,143 to Laurin et al.) Metal ions or salts have also been incorporated into polyurethane and other polymer coatings. (U.S. Pat. Nos. 5,326,567; 5,607,683; and 5,662,913 to Capelli; U.S. Pat. No. 4,592,920 to Murtfeldt; and U.S. Pat. No. 5,848,995 to Walder.
Further, a combination of metal ions and chlorhexidine have been incorporated into polymers that are used for coating medical devices. (U.S. Pat. No. 5,019,096 to Fox, Jr. et al.). Antimicrobial zeolites have also been incorporated into polymer coatings. (U.S. Pat. No. 5,003,638 to Miyake).
Thus, there is a critical need in the art for an improved coating which is not slippery when dry but becomes slippery when contacted with aqueous fluids and which will adhere to medical devices made from silicone and other difficult to coat materials.
There is also a need in the art for a coating having improved durability and uniformity which retains its wet lubricity and will adhere to medical devices made from silicone and other difficult to coat materials.
There is also a need in the art for coatings which are biocompatible and abrasion resistant, having a low wet coefficient of friction, that will adhere to medical devices made from silicone and other difficult to coat materials.
There is a further need in the art for a process of preparing elastic coatings that are lubricious when wet for medical devices made from silicone and other difficult to coat materials which is simple and efficient and results in uniformity between batches.
There is a need in the art for coatings that inhibit antimicrobial infection both on the surface of medical devices and in the surrounding tissue.
There is a further need in the art for medical devices which provide diagnostic and therapeutic effects while retaining the advantageous surface properties desired in such devices.